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Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
10:13

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Published on: June 9, 2017

Constitutively signaling G-protein-coupled receptors and human disease

L Arvanitakis1, E Geras-Raaka, M C Gershengorn

  • 1Molecular Virology Laboratory, Hellenic Pasteur Institute, Athens, Greece.

Trends in Endocrinology and Metabolism: TEM
|April 15, 2008
PubMed

Insights

G-protein-coupled receptors (GPCRs) mutations can cause diseases through loss or gain of function. Constitutively active GPCRs, including one found in a human herpesvirus, can drive tumor formation and disease.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Oncology

Background:

  • G-protein-coupled receptor (GPCR) dysregulation is linked to numerous human diseases.
  • Mutations in GPCRs can lead to loss of function or gain of function, resulting in constitutive signaling activity.
  • Constitutively active GPCRs are implicated in tumorigenesis and hyperfunction syndromes.

Purpose of the Study:

  • To investigate the role of constitutively active GPCRs in human diseases.
  • To explore the potential mechanism of viral tumorigenesis mediated by GPCRs.

Main Methods:

  • Analysis of GPCR mutations and their functional consequences.
  • In vitro and animal model studies of constitutively active GPCRs.
  • Genomic characterization of GPCRs in disease-associated viruses.

Main Results:

  • Identified GPCRs with loss of function and gain of function mutations.
  • Demonstrated that constitutively active GPCRs can be tumorigenic.
  • Characterized a constitutively active GPCR within a human herpesvirus genome.

Conclusions:

  • GPCR dysregulation, particularly constitutive signaling, is a significant factor in human disease pathogenesis.
  • Constitutively active GPCRs represent a novel mechanism for viral-induced tumorigenesis.

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